Point prevalence of evidence-based antimicrobial use among hospitalized patients in sub-Saharan Africa: a systematic review and meta-analysis

Excessive and improper use of antibiotics causes antimicrobial resistance which is a major threat to global health security. Hospitals in sub-Saharan Africa (SSA) has the highest prevalence of antibiotic use. This systematic review and meta-analysis aimed to determine the pooled point prevalence (PPP) of evidence-based antimicrobial use among hospitalized patients in SSA. Literature was retrieved from CINAHL, EMBASE, Google Scholar, PubMed, Scopus, and Web of Science databases. Meta-analysis was conducted using STATA version 17. Forest plots using the random-effect model were used to present the findings. The heterogeneity and publication bias were assessed using the I2 statistics and Egger’s test. The protocol was registered in PROSPERO with code CRD42023404075. The review was conducted according to PRISMA guidelines. A total of 26, 272 study participants reported by twenty-eight studies published from 10 countries in SSA were included. The pooled point prevalence of antimicrobial use in SSA were 64%. The pooled estimate of hospital wards with the highest antibiotic use were intensive care unit (89%). The pooled prevalence of the most common clinical indication for antibiotic use were community acquired infection (41%). The pooled point prevalence of antimicrobial use among hospitalized patients were higher in SSA. Higher use of antibiotics was recorded in intensive care units. Community acquired infection were most common clinical case among hospitalized patients. Health systems in SSA must design innovative digital health interventions to optimize clinicians adhere to evidence-based prescribing guidelines and improve antimicrobial stewardship.


SSA
Sub-Saharan Africa WHO The World Health Organization Global antibiotic consumption rates surged by 46%, indicating that the defined daily dose (DDD) per 1000 population per day rose from 9.8 to 14.3 between 2000 and 2018 1 .In low-and middle-income countries (LMICs), antibiotic usage increased by 76% and is projected to continue rising by 2030 2 .Hospitals in SSA have a higher prevalence of antibiotic usage (50%), including the use of broad-spectrum cephalosporins and penicillin 3 .With improving economies and enhanced access to pharmaceuticals, many of LMICs now revealed antibiotic consumption rates comparable to or even surpassing those of high-income countries 4 .Sub-Saharan African countries are experiencing a similar trend in antibiotic consumption, which could be exacerbated by the region's exceptionally high infectious disease burden 5 .This sharp rise in antibiotic usage with or without prescription, has become a pressing public health concern due to its strong association with the development of antimicrobial resistance in low resource clinical context 6,7 .
The misuse and overuse of antibiotics have led to increased rates of antimicrobial resistance, higher levels of morbidity and mortality, and escalated healthcare costs in low-income countries 8,9 .To address this issue, evaluating antibiotic prescribing patterns among patients in healthcare facilities is essential in identifying opportunities for antimicrobial stewardship to promote appropriate antibiotic use 10,11 .
Point prevalence studies have proven to be reliable and valid methods for measuring antibiotic use among hospitalized patients 12 .They provide crucial insights into the current state of antibiotic use within healthcare settings, aiding in the identification of patterns and deviations from recommended practices 13 .This data can inform targeted interventions to improve guideline adherence, optimize antibiotic selection, dosing, and duration, and reduce inappropriate prescriptions 14,15 .By promoting evidence-based clinical decisions, these studies contribute to the prevention of antibiotic overuse, the emergence of antimicrobial resistance, and the enhancement of patient outcomes, thus serving as a vital tool in advancing the quality and effectiveness of real-world healthcare practices 16,17 .
In sub-Saharan Africa, several point prevalence studies have reported a high rate of antibiotic use among hospitalized patients, along with inappropriate usage in healthcare facilities 18 .However, there is limited regionallevel data available to describe the point prevalence of antibiotic use among hospitalized patients in SSA 19 .Understanding the epidemiology of antibiotic use in this context and assessing the quality of antibiotic prescribing are critical steps in designing effective antimicrobial stewardship interventions aimed at encouraging the rational use of antibiotics and improving clinical outcomes for patients 20 .Therefore, this systematic review and meta-analysis aimed to determine the pooled point prevalence of antibiotic use among hospitalized patients in sub-Saharan Africa.

Search strategy and selection of studies
The search strategy aimed to find both published and unpublished literature.Initially, a preliminary search was conducted on the Google Scholar to identify indexed full texts or metadata of scholarly literature on the topic.We adapted key terms as needed for each database, utilizing a combination of MeSH terms and text words, employing Boolean operators "AND" and "OR" for searches in databases like CINAHL, PubMed, EMBASE, Scopus, and Web of Science (Appendix I).Additionally, we examined the reference lists of selected studies for potential additional sources.No restrictions were imposed based on language or publication year.After the search, all identified citations were organized and imported into EndNote version 15.0, with duplicates removed.Two independent reviewers (MTB and BH) screened titles and abstracts, and a third reviewer (ZEK) cross-checked them against the inclusion and exclusion criteria.Relevant studies meeting the criteria were obtained in full, along with their citation details.Studies reporting the point prevalence of antibiotic use among hospitalized patients in SSA, which were published from 2013 to 2023 were eligible for inclusion.Excluded were systematic reviews, Studies having participants sampled inappropriately and the setting not described in detail studies, data analysis not conducted with sufficient coverage of the identified sample, and literature from high-income countries.Two independent reviewers (MTB and BH) assessed the full text of selected citations against the inclusion criteria, with a third reviewer (LWT) conducting a double-check.Reasons for excluding studies failing to meet the inclusion criteria upon full text review were documented.Any disagreements between reviewers at each stage of the study selection process were resolved through discussion or by consulting a third reviewer.The PRISMA checklist (Appendix II) and flow chart was used to describe the matching pages in the manuscript with the number of articles identified, included, and excluded with justifications.The results of the search were fully reported in the final systematic review and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram (Fig. 1) 21 .

Operational definitions
Point prevalence survey of antimicrobial use Is a structured assessment done in healthcare settings to determine the percentage of patients receiving antimicrobial treatment at a particular moment 22 .Its goal is to assess the appropriateness of antimicrobial use, including choice, dosage, and duration, to enhance antimicrobial stewardship practices and combat antimicrobial resistance, ensuring effective and sustainable use of these essential medications 23,24 .

Data extraction
The data were extracted from included studies using the data extraction tool prepared by MTB.The tool includes variables such as the name of the author, publication year, study design, data collection period, sample size, study area, and the point prevalence of antimicrobial use.The data extraction tool contains information on the indication for antibiotic use; prevalence of antibiotic use in different wards, classes of antibiotics used, types of antibiotics used, and AWaRe classification.BH extracted the data, and LWT and MTB cross-checked the extracted data for its validity and cleanness.Authors of papers were contacted to request missing or additional data.

Data quality and risk of bias assessment
Eligible studies were critically appraised by two independent reviewers (MTB and BH).Full texts screening including the methodological quality assessment were examined using the JBI's critical appraisal instrument for prevalence studies 29 .Studies that fulfill at least seven out of the nine domains of the JBI criteria questions were eligible for meta-analysis.The results of the critical appraisal were reported in narrative form and a table.A lower risk of bias (94%) observed after assessment (Appendix III).Studies with inadequate sample size, inappropriate sampling frame and poor data analysis were excluded.Articles were reviewed using titles, abstracts, and full text screening.

Indications for antibiotic prescription among hospitalized patients in SSA
Community-acquired infection ranged from 27.7 to 61%, surgical antibiotic prophylaxis ranged from 14.6 to 45.3%, hospital-acquired infections ranged from 1.2 to 40.3%, and, medical prophylaxis ranged from 0.5 to 29.1% were the most common clinical indications (Table 5).Antibiotic prescription for 938 inpatients were done for unknown clinical indications (Table 5).

Pooled point prevalence of evidence-based use of antibiotics in SSA
The pooled point prevalence of evidence-based use of antimicrobials were 64.15% (95%CI: 58.31-69.79%)(Fig. 2).
Visual funnel plots asymmetry examination and Egger's regression tests revealed that there was no publication bias 67 .

Discussion
This systematic review and meta-analysis aimed to determine the pooled point prevalence of evidence-based antimicrobial use among hospitalized patients in sub-Saharan Africa.A total of 26, 272 patients admitted to twenty-eight hospitals of ten countries in SSA were included.The pooled point prevalence of antimicrobial use at point of care was 64%.The finding of this study is higher than the antibiotic use in hospitals of Middle East (28.3%) 68and Europe (30.5%) 69.This could be attributed to misuse and overuse of antibiotics 70,71 , poor infection and disease prevention and control 72 , and, water, sanitation and hygiene practice in health-care facilities 73 , and poor surveillance of antimicrobial resistance in SSA 74,75 .The pooled point prevalence of antibiotic use in intensive care unit of hospitals in SSA were 89%.This finding is higher than a point prevalence of use of antimicrobials in ICUs in the United States 62.2% 76 and Poland 59.6% 77 .
The uses of antimicrobials at point of care in surgical and medical wards were 58% and 54% in SSA.The overuse or inappropriate use of antimicrobials at the point of care in medical and surgical wards can lead to antibiotic resistance 8 , which can make infections harder to treat.Moreover, unnecessary antimicrobial use can disrupt the balance of the microbiome, leading to complications like Clostridium difficile infections 78 .The pooled estimate of antibiotics used by inpatients admitted to obstetrics and gynecology wards of the hospitals in SSA were 46%.www.nature.com/scientificreports/ The finding of this study was higher than the antibiotic consumption in obstetrics and gynecology departments of Peruvian hospital 31% 79 .Higher antibiotic use in obstetrics and gynecology wards in SSA can be attributed to factors such as a higher prevalence of surgical procedures 80 , which often require prophylactic antibiotics to prevent post-operative infections 81 .Additionally, cases of infections related to childbirth, such as postpartum infections or complications following gynecological procedures, may necessitate antibiotic treatment in SSA 82,83 .
The pooled prevalence of community and hospital acquired infections in SSA were 41% and 11.15% respectively.The pooled estimate of this review was higher than a study in East Africa that reported 34% CAI 84 .This could be due to non-standardized antibiotic use in SSA.Our review result revealed that HAI in SSA were lower than the finding from LMICs 17.9% 85 .
The misuse of antibiotics in both community and hospital-acquired infections has far-reaching consequences 86 .In the community, inappropriate antibiotic use contributes to the development of antibioticresistant bacteria, rendering infections harder to treat and increasing healthcare costs 87,88 .Patients may experience treatment failures, longer hospital stays, and increased mortality rates 89 .Moreover, the continued misuse of antibiotics fuels the global crisis of antibiotic resistance, jeopardizing the effectiveness of these essential drugs for future generations 90,91 .In hospital settings, similar consequences are exacerbated by the potential for widespread outbreaks of antibiotic-resistant infections among vulnerable patients 92 .The resulting challenges in managing infections can strain healthcare systems, diminish the success of medical interventions, and underscore the critical need for stringent antibiotic stewardship practices to preserve the efficacy of antibiotics.
The pooled prevalence of the most common clinical indications for antibiotic use in hospitals of SSA were community acquired infection (40.99%), surgical prophylaxis (28.54%), medical prophylaxis (11.86%), and hospital acquired infection (11.15%).
This study revealed that the pooled prevalence of HAI (11.15%) is lower than the global estimate (14%) 93 .This could be attributed to inadequate infection control measures 94 , limited resources 95 , overcrowding 96 , and a higher burden of infectious diseases 97 .Poor sanitation and healthcare infrastructure can contribute to the increased risk of infections within healthcare facilities in SSA 98 .
According to this study, the pooled estimate of surgical prophylaxis is higher than Europe (16.8%) 99and the global surgical antibiotic prophylaxis at point of care (22.8%) 17 .The surgical prophylaxis in SSA is lower than a study reported in Myanmar (34.3%) 100 .Higher surgical antibiotic prophylaxis may be attributed to surgeon's overuse of antibiotics to mitigate infection risks in environments with higher prevalence of surgical site infections and limited access to post-operative care in SSA [101][102][103] .Surgeons may also lack awareness of appropriate guidelines, and patients may expect antibiotics due to a perception of their effectiveness 103 .
The pooled point prevalence of medical prophylaxis in this study is lower than European region (24.9%) 69nd Indonesia (47.1%) 104 .A lower point prevalence of medical prophylaxis in SSA suggests limited access and utilization of preventative medical interventions 105 .This may be indicative of healthcare system challenges, resource constraints, or insufficient awareness and education 106,107 .It can result in a higher disease burden, increased healthcare costs, and potentially poorer clinical and public health outcomes for the population 10,108 .

Conclusion
The pooled point prevalence of antimicrobial use among hospitalized patients were higher in SSA.Higher use of antibiotics in intensive care unit, surgical, medical, and obstetrics and gynecology wards of hospital in SSA were recorded.Community acquired infection, surgical and medica prophylaxis, and hospital acquired infection were clinical indications reported to have the highest to lowest pooled point prevalence of antibiotics used.Health systems in SSA must design innovative interventions to optimize clinicians adhere to evidence-based prescribing guidelines and improve antimicrobial stewardship.

Implications for evidence-informed policy and clinical practice
A higher pooled point prevalence of antimicrobial use in sub-Saharan Africa implies a need for immediate policy and clinical practice interventions.Policymakers should prioritize allocation of scarce resources for antimicrobial stewardship programs and infection control measures.Innovative intervention must be in place to optimize clinicians adhere to evidence-based prescribing guidelines to combat antimicrobial resistance, reduce adverse effects, and improve patient outcomes.Health systems in sub-Saharan Africa must emphasize the importance of leveraging clinical decision support digital health interventions to augment evidence-based antimicrobial stewardship.This evidence synthesis informs the policy decision makers to encourage the implementation of such tools to guide clinicians in evidence-based antimicrobial prescribing, reducing inappropriate use, combating resistance, and improving patient care in the context of resource constrained health system.Clinicians can benefit from real-time patient information, aiding in evidence-based prescribing and infection control efforts, significantly improving patient care.Collaboration between policymakers, clinicians, and healthcare facilities is crucial to mitigate the impact of these issues on public health.

Figure 2 .
Figure 2. The pooled point prevalence of evidence-based use of antibiotics among hospitalized patients in sub-Saharan Africa.

Figure 3 .Figure 4 .
Figure 3.The pooled point prevalence of evidence-based use of antibiotics in intensive care units in hospitals of sub-Saharan Africa.

Figure 5 .
Figure 5.The pooled point prevalence of evidence-based use of antibiotics in obstetrics and gynecology wards in hospitals of sub-Saharan Africa.

Figure 6 .
Figure 6.The pooled point prevalence of evidence-based use of antibiotics in surgical wards in hospitals of sub-Saharan Africa.

Figure 7 .
Figure 7.The pooled prevalence of evidence-based use of antibiotics for community acquired infections in hospitals of sub-Saharan Africa.

Figure 8 .Figure 9 .
Figure 8.The pooled prevalence of evidence-based use of antibiotics for hospital acquired infections in hospitals of sub-Saharan Africa.

Figure 10 .
Figure 10.The pooled prevalence of evidence-based use of antibiotics for surgical prophylaxis in hospitals of sub-Saharan Africa.

Figure 11 .
Figure 11.The pooled prevalence of evidence-based use of antibiotics for unknown clinical indications in hospitals of sub-Saharan Africa.

Table 1 .
Characteristics of included studies in the meta-analysis to assess point prevalence of evidence-based antibiotic use among hospitalized patients in sub-Saharan Africa.ECDC, European Center for Diseases Prevention and Control; CAI, community acquired infection; HAI, hospital acquired infection; ICU, intensive care unit; PICU, pediatric intensive care unit; NICU, neonatal intensive care unit; PPS, point prevalence survey.

Table 2 .
Antibiotic use by wards among hospitalized patients in sub-Saharan Africa.AU, antibiotic use.

Table 3 .
Most commonly used antibiotics among hospitalized patients in sub-Saharan Africa.

Table 5 .
Clinical indications for which antibiotics were prescribed for hospitalized patients in sub-Saharan Africa.